Preparation of hydroxyalkylpiperazinones by reacting glyoxal with hydroxyalkyldiamines

ABSTRACT

A process for the preparation of 4-(2-hydroxyalkyl)-2-piperazinones and their substituted derivatives comprising reacting an N-hydroxyalkylalkylenediamine, e.g.2-[(2-aminoethyl)amino]ethanol, or a hydrocarbyl substituted derivative thereof with an α,β-dicarbonyl compound, e.g. glyoxal, an alkyl-substituted derivative of glyoxal or a glyoxal equivalent. Certain hexahydro-4-(hydroxyalkyl)-2H-1,4-diazepin-2-ones have been made which are new compounds.

BACKGROUND OF THE INVENTION

The present invention pertains to 4-(2-hydroxyalkyl)-2-piperazinones,hexahydro-4-(hydroxyalkyl)-2H-1,4-diazepin-2-ones and their substitutedderivatives. The 4-(2-hydroxyalkyl)-2-piperazinones have been preparedby reacting the appropriate 2-piperazinone or 3-substituted alkyl- oraryl-2-piperazinones with ethylene oxide or ethylene chlorohydrin. Thisearly research is disclosed in Chimie Therapeutique, May-June, 1969, No.3, pp. 167-173 and in U.S. Pat. No. 2,633,467. The substituted4-(2-hydroxyethyl)-2-piperazinones include compounds such as4-(2-hydroxyethyl)-3-methyl-2-piperazinone and4-(2-hydroxyethyl)-3,3-diphenyl-2-piperazinone and the like alkyl andaryl substituted 2-piperazinones.

The present invention provides a more economical route for thepreparation of the subject compounds in that it is not necessary to makethe piperazinone starting reactant of the known art.

SUMMARY OF THE INVENTION

A new method has been discovered for the preparation of4-(2-hydroxyalkyl)-2-piperazinones and their substituted derivatives.These are prepared by reacting an N-hydroxyalkylalkylenediamine or ahydrocarbyl substituted derivative thereof with an α,β-dicarbonylcompound such as glyoxal, an alkylsubstituted derivative of glyoxal or aglyoxal equivalent. The term "hydrocarbyl" employed herein means anyalkyl, cycloalkyl, aromatic, aralkyl or alkaryl radical.

The reaction of the above α,β-dicarbonyl-type reactants with certain ofthe N-hydroxyalkylalkylenediamines or their hydrocarbyl substitutedderivatives has produced a new class of cyclic amides. These amides areprepared by reacting certain N-hydroxyalkylpropanediamines or theirsubstituted derivatives with the α,β-dicarbonyl compounds. The newamides are hexahydro-4-(2-hydroxyalkyl)-2H-1,4-diazepin-2-ones.

The hydroxyalkylpiperazinones and hexahydro(hydroxyalkyl)diazepinonesmade by the process of the invention are useful as acid corrosioninhibitors. Some of the products of the invention are useful as adhesionpromoters. The use of certain of the products of the invention asregenerative solvents for the desulfurization of flue gas is describedand claimed in a separate co-filed application entitled "Sulfur DioxideRemoval from Gas Streams Using Hydroxyalkyl Substituted Piperazinones",identified as Ser. No. 085,432.

DETAILED DESCRIPTION OF THE INVENTION

Suitable hydroxyalkylalkylenediamines to be reacted with glyoxal or itsderivatives include those having the formula ##STR1## wherein R ishydrogen or an alkyl group of 1 or 2 carbon atoms, R₁ is hydrogen, analkyl group of 1-6 carbon atoms or an aryl or an aralkyl group havingfrom 6 to 12 carbon atoms and R₂ is hydrogen, an alkyl or hydroxyalkylgroup of 1-6 carbon atoms or an aryl or an aralkyl group having from 6to 12 carbon atoms and n is 1 or 2.

Especially suitable hydroxyalkylalkylenediamines for the reactioninclude 2-[(2-aminoethyl)amino]ethanol(AEEA),2-[(3-aminopropyl)amino]ethanol, 2-[(2amino-1-methylethylpropyl)aminoethanol(APAE), 2-[(2-amino-1,1-dimethylethyl)amino]ethanol,2-[(2-amino-2-methylpropyl)amino]ethanol, 2-[[b2-(methylamino)ethyl]amino]ethanol,2-[[2(ethylamino)ethyl]amino]ethanol,2-[(2-amino-1-phenylethyl)amino]ethanol,2-[[2-(phenylamino)ethyl]amino]ethanol,2,2'-(1,2-ethanediyldiimino)bisethanol,1-[(2-aminoethyl)amino]-2-propanol, 1-[(3-aminopropyl)amino[-2-propanol, 1-[(2-aminopropyl)amino]-2-propanol,1-[(2-aminoethyl)amino]-2-butanol, and the like or mixtures thereof.

Suitable α,β-dicarbonyl compounds are those having the formula ##STR2##wherein R and R₁ have been previously defined and R₃ is hydrogen or analkyl group having from 1-4 carbon atoms.

The preferred α,β-dicarbonyl compounds are glyoxal, pyruvaldehyde(methyl glyoxal), 1,2butanedione, 1,2-pentanedione, and the like andmixtures thereof. Other compounds which are equivalent to glyoxal or itsderivatives are glyoxal dihydrate, dilute aqueous solutions of glyoxal,e.g. 40%, glyoxal hydrogen sulfite, alkali metal di-salts of 1,2-dihydroxy-1,2-ethanedisulfonic acid and 2,3-dihydroxy-1,4-dioxane andits alkyl derivatives. The hydrogen sulfite derivative of glyoxal whentreated with a base liberates glyoxal. The preparation of the dihydroxydioxane is described in Synthesis by M. C. Venuti, 1982, Thieme-StrattonInc., New York, p. 62, the same being incorporated herein by reference.

The 4-(2-hydroxyalkyl)-2-piperazinones which can be made according tothe process of the invention include those of the formula: ##STR3##wherein R is hydrogen or an alkyl group having 1 or 2 carbon atoms, R₁is hydrogen, an alkyl group having 1 to 6 carbon atoms or an aryl or anaralkyl group having from 6 to 12 carbon atoms and R₂ is hydrogen, analkyl or hydroxyalkyl group having from 1 to 6 carbon atoms or an arylor aralkyl group having from 6 to 12 carbon atoms.

The 4-(2-hydroxyalkyl)-2-piperazinones include4-(2-hydroxyethyl)-2-piperazinone,4-(2-hydroxyethyl)-1-methyl-2-piperazinone,4-(2-hydroxyethyl)-3-methyl-2-piperazinone,4-(2-hydroxyethyl)-5-methyl-2-piperazinone,4-(2-hydroxyethyl)-6-methyl-2-piperazinone,3-ethyl-4-(2-hydroxyethyl)-2-piperazinone,6-ethyl-4-(2-hydroxyethyl)-2-piperazinone,4-(2-hydroxyethyl-2-piperazionone, dimethyl-2-piperazinone,1-ethyl-4-(2-hydroxyethyl-)5,6-piperazinone,4-(2-hydroxyethyl)-3-phenyl-2-piperazinone,1,4-bis(2-hydroxyethyl)-2-piperazinone, 4-(2-hydroxypropyl)-2-piperazinone, 4-(2-hydroxybutyl)-2-piperazinone, and4-(2-hydroxypropyl)-6-methyl-2-piperazinone.

Hexahydro-4-(hydroxyalkyl)-2H-1,4-diazepin-2- ones include, for example,those of the formula: ##STR4## wherein R is either hydrogen or an alkylgroup having 1 or 2 carbon atoms, R₁ is hydrogen, an alkyl group having1 to 6 carbon atoms or an aryl or aralkyl group having from 6 to 12carbon atoms and R₂ is hydrogen, an alkyl or hydroxyalkyl having 1 to 6carbon atoms and aryl or aralkyl having 6 to 12 carbon atoms.

Such hexahydro-4-(hydroxyalkyl)-2H-1,4-diazepin-2-ones includehexahydro-4-(2-hydroxyethyl)2H-1,4-diazepin-2-one,hexahydro-4-(2-hydroxyethyl)-1-methyl-b 2H-1,4-diazepin-2-one,hexahydro-4-(2-hydroxyethyl)-3-methyl-2H-1,4-diazepin-2-one,hexahydro-4`-(2-hydroxyethyl)hydro-4-(2-hydroxyethyl)-5-methyl-2H-1,4-diazepin-2-one,5-ethyl-hexahydro-4-(2-hydroxyethyl)-2H-1,4- diazepin-2-one,hexahydro-4-(2-hydroxyethyl)-7-methyl-2H-1,4-diazepin-2-one,7-ethyl-hexahydro-4-(2-hydroxyethyl) -2H-1,4-diazepin-2-one,hexahydro-4-(2-hydroxy-ethyl)-5,7-dimethyl-2H-1,4-diazepin-2-one,hexahydro-4-(2-hydroxyethyl)-7,7-dimethyl-2H-1,4-diazepin-2-one,hexahydro-4-(2-hydroxyethyl)-7-phenyl-2H-1,4-diazepin-2-one,hexahydro-4-(2-hydroxypropyl)-2H-1,4-diazepin-2-one,hexahydro-4-(2-hydroxybutyl)-2H-1,4-diazepin-2-one,hexahydro-4-(2-hydroxypropyl)-7-methyl-2H-1,4- diazepin-2-one.

Suitable solvents which can be employed in the reaction are water,alcohols, ethers and the like. Particularly suitable solvents include,water, methanol and ethanol, water being preferred. A solvent is notindispensable, but it minimizes the heat of reaction. Usually 20 to 70%of the N-hydroxyalkylalkylenediamine is reacted with 20 to 40% ofglyoxal or its substituted derivative in a solvent.

The reaction can be carried out at a temperature between about 0° andabout 200° C. Preferably, the reaction is conducted between about 80°and about 100° C. Below 80° C. the product requires long reaction times,otherwise the amount obtained is too small to be of practical value.

The N-hydroxyalkylalkylenediamine and glyoxal, its alkyl-substitutedderivative or glyoxal equivalent can be employed in quantities whichprovide a mole ratio of the diamine to the glyoxal of from about 0.75:1to about 4:1, preferably from about 1:1 to about 2:1.

The crude reaction product can be purified by vacuum distillation,solvent extraction, recrystallization or any combination of thesetechniques. Suitable solvents for extraction include aliphatichydrocarbons, alcohols, esters and chlorinated solvents. Particularly,suitable solvents include hexane, ethanol, isopropanol, ethyl acetate,methylene chloride and chloroform.

The products from the reaction of N-hydroxyalkylalkylenediamines, ortheir substituted derivative, with glyoxal, its alkyl-substitutedderivatives or glyoxal equivalent are useful as hydrochloric acidcorrosion inhibitors and adhesion promoters. These products also act asbinders between asphalt and fiberglass and between asphalt and rockaggregate, comparing favorably with commercial binder products.

The following examples are representative of the process, its products,their purification and use.

EXAMPLE 1

Into a resin kettle, equipped with a reflux condenser, addition funnel,immersion thermometer, mechanical stirrer and nitrogen purge system, isplaced 802 g (7.7 moles) 2-[(2-aminoethyl)amino]ethanol dissolved in 347g water. The contents in the resin kettle are stirred under nitrogenbetween 0° and 20° C., using an ice bath. 279 g of 40 wt. % glyoxal inwater (1.92 moles) is diluted further with 94 g water and added dropwiseto the reactor contents over a period of forty-five minutes. The reactorcontents are allowed to stir at ambient temperature for fifteen minutes.Residual 2-[(2-aminoethyl)amino]ethanol and water are removed by vacuumdistillation at 250° C. and 10 mm Hg. Infrared spectroscopy supports thepresence of 4-(2-hydroxyethyl)-2-piperazinone (4-HEP).

EXAMPLE 2

A 32 wt. % aqueous solution of glyoxal (232 g, 4.0 moles) is addeddropwise to a stirred chilled (5° C.) 70 wt. % aqueous solution of2-(2-aminoethyl)amino]ethanol (312 g, 3 moles) in a nitrogen atmosphere.The rate of addition of the aqueous solution of glyoxal is controlled sothat all the solution is added within 1 hour 42 minutes, with a maximumrise in temperature to 23° C. Twelve days later, the water is removedfrom the reaction product of glyoxal and 2-(2-aminoethyl)amino]ethanolby rotary evaporation at 100° C. To insure the removal of all water,isopropanol is added to the reaction product and is removed by rotaryevaporation at 100° C. The product from the reaction of glyoxal and2-[(2-aminoethyl)amino]ethanol is a sticky, black solid. The product isidentified by electron impact mass spectroscopy and is shown to be 89%(area) 4-HEP by flame ionization gas chromatography.

EXAMPLE 3

A 30 wt. % aqueous solution of glyoxal (405 g, 7 moles) is addeddropwise to a stirred chilled (22° C.) 70 wt. % aqueous solution of2-[(2-aminoethyl)amino]ethanol (729 g, 7 moles) in a nitrogenatmosphere. The rate of addition of the aqueous solution of glyoxal iscontrolled so that all the solution is added within 6 hours and 14minutes with a maximum rise in temperature to 31° C. The reactionproduct is subjected to rotary evaporation under full vacuum at boilingwater temperature. The rotary evaporation bottoms are poured into a feedand degasser flask and subjected to wiped-film distillation at atemperature between 200° and 255° C. and a pressure of 1 mm Hg in a2"-diameter Pope wiped-film still. A yellowish-brown, viscous liquid iscollected in the distillate receiver. This liquid is dissolved in excess1-propanol and a water-propanol azeotrope removed by fractionaldistillation at 70° C. at 100 mm Hg. Pressure is reduced to 5 mm Hg andthe temperature maintained at 70° C. for 2 hours. The viscous liquid isdissolved in the minimum amount of dry acetonitrile at 60° C.; the flaskis capped to exclude water and chilled to 4° C. and held there for 24 to72 hours. Solids are removed by filtration under a nitrogen pad. Whitecrystals of 4-HEP are obtained when the solids are recrystallized at 50°C. from a minimum amount of acetone. The crystals of 4-HEP melt at 59.5to 60° C. and boil at 450° C. and are shown to be 99+% pure4-(2-hydroxyethyl)-2-piperazinone by capillary gas chromatography.

EXAMPLE 4 Preferred Method of Making a Hydroxyalkylpiperazinone

A 2 liter resin kettle, equipped with a dropping funnel, thermometer,temperature controller, nitrogen sparge tube, mechanical stirrer, and achilled water condenser, is charged first with 730 g of deionized waterand then 218 g (2.1 moles) of AEEA. Heat was provided by two heat lamps.

There is a mild exotherm due to the heat of solution of AEEA. Thestirrer and nitrogen sparge (10 mL/minute) are started and the solutionis heated to 100° C. Aqueous glyoxal (20%, 552 grams, 2.00 moles) isadded dropwise over three hours. Gas chromatographic analysis shows thatthe reaction is essentially complete when the glyoxal addition iscomplete. The heat is removed and 1200 grams of charcoal (NORIT A) isadded. The reaction mixture is stirred overnight at ambient temperature,then filtered to remove the charcoal. Gas chromatographic analysis shows4-HEP to be present in 93% yield.

The following example illustrates a method for preparing one of the newclass of amides, specificallyhexahydro-4-(2-hydroxyethyl)-2H-1,4-diazepin-2-one.

EXAMPLE 5

A 70 wt. % methanolic solution of 1,3-diaminopropane (715.9 g, 9.7moles) is added to a resin kettle equipped with a dry ice condenser,immersion thermometer, mechanical stirrer and a sample line consistingof two 3000-lb check valves with 0.5-1 psi cracking pressure and aneedle valve. The sample line is connected to a cylinder of ethyleneoxide. The ethylene oxide (63.6 g, 1.45 moles) is introduced and reactedat a temperature between 0° and 5° C. The methanol and unreacted1,3-diaminopropane are removed by rotary evaporation. The yield of2-[(3-aminopropyl)amino]ethanol (APAE)is 84%.

A 70 wt. % aqueous solution of the above prepared APAE (144.8 g, 1.23moles) is added to a resin kettle equipped with a reflux condenser,immersion thermometer, mechanical stirrer, addition flask and nitrogenpurge system. A 30 wt. % aqueous solution of glyoxal (71 g, 1.23 moles)is added dropwise to the stirred chilled (2° C.) aqueous solution of2-[(3-aminopropyl)amino]ethanol in a nitrogen atmosphere. The rate ofaddition is controlled so that all the aqueous solution of glyoxal isadded within one hour, with a maximum rise in temperature of 20° C.Water is removed at 100° C. by rotary evaporation. Electron impact andchemical ionization mass spectroscopy and infrared spectroscopyindicates the reaction product to behexahydro-4-(2-hydroxyethyl)-2H-1,4-diazepin-2-one.

An alternative method of making 4-HEP is to use2,3-dihydroxy-1,4-dioxane in place of glyoxal. The following exampleillustrates this method.

EXAMPLE 6

AEEA (0.1 moles) is added to a stirred solution of2,3-dihydroxy-1,4-dioxane (0.1 mole) in 300 mL of 95% ethanol at 35° C.in a 500 mL Erlenmeyer flask. Potassium carbonate (0.1 mole) was presentas catalyst. The solution was heated and stirred at 35° C. for ˜6 hours,then allowed to stand overnight at room temperature. gc/ms analysisshowed that 4-HEP was present.

The following examples illustrate the utilities of some of the productsof the process of the invention.

EXAMPLE 7 Corrosion Inhibition Test

To show a utility for the products of the reaction, the product ofExample 2 is tested as a corrosion inhibitor. Two tenths of a percent of4-(2-hydroxyethyl)-2-piperazinone, a 1010 carbon steel coupon and 100grams of 10% hydrochloric acid are added to a test tube which is placedin a one-liter Parr bomb and heated for 6 hours at 175° F. The coupon isremoved from the bomb, cleaned with 18.5% inhibited HCl, washed anddried. The corrosion rate is calculated according to the followingformula: ##EQU1##

The density is expressed in g/cc, the surface area in sq.in., the timeof the test in hrs. and the rate in mils/year (mpy). The percentprotection provided by the inhibitor is calculated as follows: ##EQU2##

The 4-HEP provided 88% protection against acid corrosion. Dowell A-120and A-250, two commercial inhibitors at the same concentration, exhibit97 and 99+% protection against acid corrosion, respectively.

EXAMPLE 8 Asphalt Binder Test

Another utility is discovered as a result of the observed adhesiveproperties of the piperazinones. The Firestone modification of ASTM2138-H test (cord pullout adhesion) is used to evaluate binders betweenasphalt and fibre glass. The 4-HEP exhibits better cord pullout adhesionthan a control with no binder and slightly better cord pullout thanamino silanes available commercially from Union Carbide and Dow Corning.Thus, 4-HEP is a slightly better adhesive for asphalt than the aminosilanes.

EXAMPLE 9 Rock Aggregate Anti-strip Test

The 4-HEP exhibits better adhesion than the control and all othercompounds tested as asphalt antistrip agents for rock aggregate. Theamino silanes and Ethyleneamine E-100 are among the other compoundstested as asphalt anti-strip agents. In the rock aggregate test, theaggregate is coated with a 5% solution of the anti-strip agent until a3-5 wt. % pickup is realized. No anti-strip agent is coated on the rockaggregate for the control. Asphalt is applied at five grams per 1000grams of the binder-coated rock aggregate. The asphalt-coated rockaggregate is heated in an oven for 2 hours at 80° C. and then subjectedto boiling water for another hour. The effectiveness of the differentanti-strip agents is determined by the observation of several persons.No quantitative data is obtained because of inaccuracies due to someasphalt sticking to the sides of the beaker in the boiling test.

We claim:
 1. A compound having the formula ##STR5## wherein R ishydrogen or an alkyl group having 1 or 2 carbon atoms, R₁ is hydrogen,an alkyl group having 1-6 carbon atoms, an aryl or aralkyl group havingfrom 6 to 12 carbon atoms, and R₂ is hydrogen, an alkyl or hydroxyalkylgroup having 1 to 6 carbon atoms and an aryl or aralkyl group having 6to 12 carbon atoms.
 2. The compound of claim 1 wherein R, R₁ and R₂ eachis hydrogen.
 3. The compound of claim 1 wherein R, and R₁ each ishydrogen and R₂ is hydroxyalkyl.
 4. The compound of claim 3 wherein thehydroxyalkyl group is hydroxyethyl.
 5. The compound of claim 1 wherein Rand R₁ each is hydrogen and R₂ is alkyl.
 6. The compound of claim 5wherein the alkyl group is methyl or ethyl.
 7. The compound of claim 1wherein R, and R₂ each is hydrogen and at least one R₁ is alkyl.
 8. Thecompound of claim 1 wherein the alkyl group is methyl or ethyl.